Background
To date, information on risk factors and temporal patterns of recurrences in patients with vulvar cancer is sparse. Conclusive data for an optimal surveillance strategy are lacking.
...Methods
This multicenter, retrospective population-based register study included 1412 patients who have been treated from 2000 to 2017 for vulvar cancer in the German districts of Upper Palatinate, Lower Bavaria, and Saxony-Anhalt. Kaplan–Meier method, and univariate and multivariate Cox regression were employed to evaluate prognostic factors and temporal course of overall survival, cumulative recurrence, and recurrence-free survival rates.
Results
After exclusion, the final study cohort comprised 829 patients. Most recurrences occurred within the first 3 years after diagnosis. Notably, a significant subset of patients were recurrent even after 5 years. The cumulative recurrence rate from all relapses was 18.6% 1 year after primary diagnosis. The recurrence rate increased to 34.7% after 3, to 41.8% after 5, and to 56.6% after 10 years post-diagnosis. The risk of relapse was significantly increased in patients over 70 years of age (hazard ratio (HR) = 2.7;
p
< 0.001; 95% CI 1.6–4.4), and in patients with positive nodal status N1 (HR = 2.0;
p
= 0.019; 95% CI 1.1–3.5) and N2/3 (HR = 2.2;
p
= 0.033; 95% CI 1.1–4.4).
Conclusion
Our study provides compelling evidence that follow-up care should be carried out for longer than 5 years, especially for high-risk patients.
Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in breast cancer and predicts response to anti-HER2 therapy in breast cancer. ...The prognostic relevance of moderate expression of HER2 is unclear. Data of 9872 patients with primary nonmetastatic breast cancer from the cancer registries of Magdeburg and Halle, Germany, were analyzed retrospectively. A total of 5907 patients with complete data sets including follow-up were eligible for analysis. HER2 status was determined as recommended by international guidelines. Of 5907 patients investigated, 5023 (68.4%) had HER2 0 and 1+ expression and 884 (12.0%) had HER2 (2+)/HER2− expression. Patients with hormone receptor positive (HR+) and HER2 (2+) tumors had a shorter median disease-free survival (DFS; P<0.0001) and breast cancer specific survival (BCSS; P=0.019) than HR+ patients with HER2 (0/1+) tumors. Among patients with HR− breast cancer there was no significant difference between HER2 (2+) and HER2 (0/1+) tumors. In multivariate analysis after adjustment for other prognostic factors, HER2 (2+) status remained an unfavorable prognostic factor for DFS (hazard ratio (HR)=1.217, 95% CI=1.052–1.408; P=0.008) but not for BCSS (HR=1.045, 95% CI=0.926–1.178; P=0.474). The HER2 (2+) status is an unfavorable prognostic factor for survival of patients with HR+ breast cancer. The impact of anti-HER2 therapy in this group of patients should be evaluated.
Background
The lymphadenectomy in the treatment of endometrial cancer is a topic of ongoing debate. The direct comparison between no lymphadenectomy, pelvic lymphadenectomy, and pelvic/para-aortic ...lymphadenectomy regarding overall survival of patients with endometrial cancer is missing.
Methods
We performed a multicenter, retrospective, registry-based study of 1502 patients with endometrial cancer treated with no lymphadenectomy (
n
= 697), systemic pelvic lymphadenectomy (
n
= 543) and systemic pelvic/para-aortic lymphadenectomy (
n
= 262). The patients were divided into three groups of recurrence risk: low, intermediate, and high. The outcome measure was overall survival.
Results
Median follow-up was 78 months. Lymphadenectomy did not improve overall survival of patients with low risk of recurrence. The survival effect of systemic lymphadenectomy was significant in patients with intermediate and high risk of recurrence. Multivariate analysis showed that both pelvic (HR 0.63, CI 0.38–0.82,
p
= 0.001) and combination of pelvic/para-aortic lymphadenectomy (HR 0.50, CI 0.43–0.81,
p
< 0.0001) significantly reduced the mortality risk in patients with intermediate risk compared to the patients who underwent no lymphadenectomy. In patients with high risk, only combined pelvic/para-aortic lymphadenectomy (HR 0.62, CI 0.48–0.82,
p
= 0.005) was associated with decreased mortality rate compared with no lymphadenectomy. Among patients with intermediate and high risk of recurrence who did not receive any adjuvant therapy, pelvic/para-aortic lymphadenectomy significantly reduced the mortality risk (HR 0.52, CI 0.37–0.73,
p
< 0.0001) in comparison with no lymphadenectomy. This management was superior to pelvic lymphadenectomy alone. In patients with low risk of recurrence, lymphadenectomy had no effect on overall survival.
Conclusions
Pelvic/para-aortic lymphadenectomy should be performed in all patients with endometrial cancer at intermediate and high risk of recurrence.
The goal of this study was to assess the size of the ultrasound-measured margin associated with an adequate surgical margin during breast-conserving surgery (BCS). The study was designed as a ...prospective cohort study. Patients with primary invasive breast cancer undergoing BCS were included. The ultrasound-measured surgical margins were compared with the pathological margins. 147 patients were eligible for analysis. 21 (14.3 %) patients had close or positive resection margins and 13 (8.8 %) underwent a second operation. Small excision volume, multifocality, postmenopausal status, high grade tumor-associated intraductal component, and invasion of lymph vessels and lymph nodes were associated with increased risk of positive excision margins. In the study cohort, 882 Ultrasonography (US) margins were measured and a good correlation to the pathological margins was observed. Overestimation of the US-measured margins relative to the pathological margins was increased with younger age, premenopausal status, and intraductal component. The estimated positive and negative predictive values, sensitivity and specificity were 81.0, 96.2, 48.4, and 99.1 %, respectively. We found that a sonographically estimated margin of ≥4 mm was associated with an adequate pathological margin of ≥1 mm in 100 % of tumors that did not have a high grade intraductal component. However, this was not applicable for tumor-associated high grade intraductal component where a US margin of 14 mm was associated with clear pathological margins in 100 % of cases. Intraoperative ultrasonography is a safe and feasible method to obtain clear surgical margins by BCS.
Background
The treatment of patients with small (T1a/b) breast cancer is based on retrospective analysis. The influence of intrinsic tumor subtypes on patients’ outcome and treatment decision remains ...unclear.
Patients and methods
This is a prospective cohort register study including 1008 patients with small T1a/b breast cancer treated between 2003 and 2011. Tumors were grouped by biological characteristics into four different subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer (TNBC).
Results
The median follow-up time was 6.5 years. From 919 eligible patients, 408 (44.4%) were classified as luminal A, 246 (26.8%) as luminal B, 183 (19.9%) as HER2 enriched, and 82 (8.9%) as TNBC. A total of 305 (34.2%) patients were treated with systemic therapy. Patients receiving systemic therapy were significantly younger and had lymph node metastasis, higher tumor grade, negative HR, and positive HER2 status. Patients with luminal A tumors demonstrated the best survival rate which improved with systemic therapy. The survival rate of patients with luminal B cancer, HER2-enriched tumors, and TNBC improved by addition of systemic treatment. The effect of systemic treatment was significant in luminal B (
p
= 0.040) and HER2 overexpressing tumors (
p
= 0.016). The treatment effect of systemic therapy in HER2-enriched tumors remained significant even after adjustment of other prognostic factors (HR 0.43, CI 0.19–0.98;
p
= 0.047). Notably, tumor size was not associated with patients’ survival and treatment decision.
Conclusion
The treatment decision of small breast cancer should be made by biological subtype and not by tumor size or lymph node status.
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•180 breast cancer samples were analyzed by immunohistochemistry for GLO-1 expression.•GLO-1 was highly expressed in most cancers.•GlO-1 expression correlated with abundance of the ...AGE CML and VEGF as well as treatment by radiotherapy.•GLO-1 expression correlated with relapse free survival (p = 0.07) for treatment by radiotherapy.•GLO-1 mRNA correlated with inflammation (NF-kB) and oxidative stress (nrf2).
Glyoxalase-1 (GLO-1) is the key enzyme in aldehyde defence in cancer cells. We here evaluated the prognostic impact and association with clinico-pathological parameters and relapse-free as well as overall survival in tumor samples from 187 breast cancer patients. The determined GLO1-immunoreactive score (GLO1-IRS) did not correlate with parameters such as grading, size, hormone receptors or ki67. However, an association of GLO1-IRS with the advanced glycation end product Nε-(carboxymethyl)lysine (p = 0.07) and HER2 (p = 0.06), and a strong correlation with VEGF (p = 0.008) was found. In survival analysis, no significant impact of GLO-1 IRS could be deduced for all patients. However, GLO1-IRS correlated with treatment by radiotherapy (p = 0.008) and high GLO1-IRS predicted a shorter relapse free survival after radiotherapy (log-rank p = 0.067).
METABRIC- and TCGA expression-data were analyzed for correlation of regulatory genes of the NF-κB-pathway (RELA, RELB, IRAK1), the oxidative-stress associated transcription factor nrf2 (NFE2L2), the receptor for AGEs (AGER, RAGE) as well as enzymes associated with aldehyde defense. Here, RELA, RELB and NFE2L2 correlated significantly with GLO1 expression, but there were conflicting results between the two data sources.
In conclusion, GLO1 was highly expressed in cancer cells, correlated surprisingly weak with survival, but we could show a positive association with the AGE CML as well as VEGF. Gene expression data suggest a regulation of GLO-1 mRNA via both, inflammation (NF-kB) and oxidative stress (NFE2L2) in tumors.
Management of elderly women with cervical cancer Eggemann, Holm; Ignatov, Tanja; Geyken, Christina Henrike ...
Journal of cancer research and clinical oncology,
05/2018, Letnik:
144, Številka:
5
Journal Article
Recenzirano
Background
Elderly women with cervical cancer receive less therapy in comparison with their younger counterparts. The exact reason(s) for this treatment strategy remains unclear.
Patients and methods
...We performed a multicenter, retrospective registry-based study of 1559 patients with cervical cancer. The primary outcome was the reason for not performing the indicated treatment.
Results
Median follow-up was 67.8 months. A total of 956 women were eligible for analysis: 693 (64.2%) were younger than 60 years and 387 (35.8%) were aged 61 years old and older. Elderly women were more likely to have undifferentiated cervical cancer at an advanced stage. For early stage (stage IA1–IIA), tumors patients 61 years old and older were less likely to receive surgery odds ratio (OR) 0.39; 95% CI 0.20–0.77 and radiochemotherapy (OR 0.37; 95% CI 0.21–0.66) compared with the group of patients aged < 60 years. The rate of lymphadenectomy was similar in both age groups. Patients 61 years old and older with advanced stage (IIB–IV) cervical cancer were also less likely to receive surgery odds ratio (OR) 0.42; 95% CI 0.27–0.66, lymphadenectomy (OR 0.30; 95% CI 0.12–0.51) and radiochemotherapy (OR 0.31; 95% CI 0.20–0.48) compared with patients aged < 60 years. Notably, the rate of indicated but not performed therapies proportionally increased with an increase in patient age and the most important reason for this phenomenon was the failing of recommendation.
Conclusions
Elderly women with cervical cancer are undertreated and this is more likely because the therapy was not recommended.
Purpose
To evaluate the pattern of endometrial cancer recurrence according to its biological subtype in a large cohort of patients.
Patients and methods
Patients were stage eligible if they had a ...description of registry risk of recurrence status and were not primary metastatic. Data were prospectively collected. The primary endpoints were the subtype-dependent pattern and time of recurrence.
Results
The median follow-up time was 84 months. The highest 10-year recurrence-free and overall survival were seen in the group of patients at low risk of recurrence, 83.1 and 94.1%, respectively. The 10-year recurrence-free survival for intermediate and high risk group was 65.7 and 56.2%, respectively, whereas the estimated 10-year overall survival for both groups was 84.5 and 79.3%, respectively. Patients at high risk demonstrated the highest levels of disease recurrence in the first 3–4 years after diagnosis and the most common site of metastasis was the lung. In contrast, the rate of recurrence for patients at intermediate and low risk of recurrence in the first 5 years was relatively low but remained continuous up to 10 years of follow-up. Overall, the most common site of relapse was local recurrence.
Conclusion
Endometrial cancer subtypes are associated with different times and patterns of recurrence and this should be considered when determining the treatment strategy.
Recently, we have shown that the new G-protein-coupled estrogen receptor GPR30 plays an important role in the development of tamoxifen resistance in vitro. This study was undertaken to evaluate the ...correlation between GPR30 and tamoxifen resistance in breast cancer patients. GPR30 protein expression was evaluated by immunohistochemical analysis in 323 patients with primary operable breast cancer. The association between GPR30 expression and tamoxifen resistance was confirmed in a second cohort of 103 patients treated only with tamoxifen. Additionally, we evaluated GPR30 expression in 33 primary tumors and in recurrent tumors from the same patients. GPR30 expression was detected in 56.7% of the breast cancer specimens investigated and it correlated with overexpression of HER-2 (
P
= 0.021), EGFR (
P
= 0.024) and lymph node status (
P
= 0.047). In a first cohort, survival analysis showed that GPR30 was negatively correlated with relapse-free survival (RFS) only in patients treated with tamoxifen (tamoxifen with or without chemotherapy). GPR30 expression was associated with shorter RFS (HR = 1.768; 95% CI, 1.156–2.703;
P
= 0.009). In a subset of patients treated only with tamoxifen, multivariate analysis revealed that GPR30 expression is an independent unfavorable factor for RFS (HR = 4.440; 95% CI, 1.408–13.997;
P
= 0.011). In contrast, GPR30 tended to be a favorable factor regarding RFS in patients who did not receive tamoxifen. In 33 paired biopsies obtained before and after adjuvant therapy, GPR30 expression significantly increased only under tamoxifen treatment (
P
= 0.001). GPR30 expression in breast cancer independently predicts a poor RFS in patients treated with tamoxifen.
Acquired tamoxifen resistance is a significant problem in estrogen receptor positive breast cancer. In a cellular model, tamoxifen resistance was associated with increased sensitivity towards toxic ...dicarbonyls and reduced free sulfhydryl group content. We here analyzed the role of oxidative stress and glyoxalase I activity on dicarbonyl resistance and the significance of glyoxalase I expression for survival.
Reactive oxygen species were determined by 2,7-dihydrochlorofluorescein diacetate. Inhibitors for NADPH-oxidase (diphenyleneiodonium), p38 MAPK (SB203580) and ERK1/2 (UO126) were applied to investigate interactions of these signaling molecules. N-acetyl cysteine was used to evaluate the effect of oxidative stress on cell viability, which was assessed by the resazurin assay. Gene expression was analyzed by real time qRT-PCR. Glyoxalase activity was inhibited by the specific inhibitor CS-0683 and siRNA. The relevance of glyoxalase 1 mRNA abundance on survival of breast cancer patients was evaluated by the KM-plotter web interface.
α-Oxo-aldehydes caused an immediate increase in reactive oxygen species where the tamoxifen resistant cell line (TamR) responded at lower concentrations than the MCF-7 parental cell line. Inhibitor studies placed ROS production by NADPH-oxidase downstream of p38 MAPK. The antioxidant N-acetyl cysteine (NAC) increased survival, whereas glyoxalase (GLO1) inhibition increased dicarbonyl toxicity. GLO1 mRNA abundance was correlated with unfavorable prognosis of breast cancer patients.
Dicarbonyl toxicity was mediated by oxidative stress and GLO1 activity determines aldehyde toxicity in tamoxifen resistant cells.
Glyoxalases might be predictive biomarkers for tamoxifen resistance and a putative target for the treatment of tamoxifen resistant breast cancer patients.
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•Dicarbonyls evoke oxidative stress in mamma carcinoma cells.•Dicarbonlys activate NADPH-oxidase via p38 MAPK.•Dicarbonlys activate p42/44 MAPK,PKB and NF-κB via independent pathways.•Glyoxalase I activity is essential for dicarbonyl resistance.•Glyoxalase I mRNA abundance is a prognostic marker for estrogen receptor positive breast carcinoma.
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